title: Analysis of API2-MALT1 fusion, trisomies, and immunoglobulin VH genes in pulmonary mucosa-associated lymphoid tissue lymphoma.
abstract: Pulmonary mucosa-associated lymphoid tissue lymphoma is unique in that chronic inflammation is rare and that API2-MALT1 fusion, resulting from t(11;18)(q21;q21), occurs frequently. In this study, we examined 20 cases for API2-MALT1 fusion using the multiplex reverse-transcription polymerase chain reaction and looked for trisomy 3, trisomy 18, and abnormalities of MALT1 and IGH genes using fluorescence in situ hybridization. In addition, we analyzed VH genes by subcloning of the monoclonal polymerase chain reaction products. Of 20 cases studied, we detected gene abnormalities in 16: API2-MALT1 fusion in 9, trisomy 3 in 5, trisomy 18 in 4, MALT1 abnormality in 13, and IGH abnormality in 1. MALT1 gene abnormalities were concordant with API2-MALT1 fusion or trisomy 18. One case showed API2-MALT1 fusion and trisomy 3. On detection of API2-MALT1 fusion and trisomies, we were able to divide our cases into 3 groups, API2-MALT1 positive, trisomy positive, and no detectable gene abnormality, suggesting that tumor development had processed along different genetic pathways. All 20 cases were analyzed for VH genes. Most of the VH genes selected by the lymphomas belonged to the VH3 family, but there was no restriction to any particular VH fragment. Of interest, VH genes were unmutated in 7 cases, suggesting that T-cell-independent extrafollicular B-cell maturation may be important in the development of this lymphoma. In addition, both mutated and unmutated tumor cases were found to carry the API2-MALT1 fusion and trisomy 3. This observation suggests that these gene abnormalities may occur in microenvironments found before or outside of follicular germinal centers.
authors.affiliation: Department of Pathology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Xia
authors.forename: Takahisa
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sakuma
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamada
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takino
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Okabe
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiyoshi
authors.forename: Hideo
authors.initials: H
authors.lastname: Hattori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
mesh_terms: D000328:Adult; D000368:Aged; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D020169:Caspases / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014314:Trisomy; D044767:Ubiquitin-Protein Ligases
chemical_list: C415943:API2-MALT1 fusion protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein